MRI has been established as one of the imaging methods of choice for evaluation of soft tissues in the musculoskeletal system, including tendons. While this is the case, significant challenges in the diagnosis and characterization of pathology exist due to the intrinsic composition of tendon which has short transverse relaxation times (T2 value, an intrinsic MR property of tissue). On typical clinical MR pulse sequences, tendons show little or no signal. As a result the internal architecture and quantitative structural/biochemical evaluation of tendon has not previously been possible with standard clinical MRI. Ultrashort TE (UTE) pulse sequences can detect signal from tendon before it has decayed to very low levels and allow characterization of tendon morphology and infrastructure. Previously, feasibility of UTE sequences for qualitative and quantitative tissue characterization has been established. Most recently, MR techniques that combine UTE acquisition methods with sequences designed for structural (T2* and T2) and biochemical (T1r) analysis of tissue has been developed. These factors are important to determine functional integrity and these non-invasive analytic techniques could be a powerful tool in the management of tendon disease. The purpose of this study is to optimize these novel UTE sequences, validate them, and translate the technology to clinical use to improve the diagnosis and monitoring of damaged tendons due to acute trauma, repetitive strain injuries, and acquired or inherited diseases. To accomplish this, cadaveric specimens will be used for optimization and validation. During this stage, UTE sequences will be compared to standard clinical sequences as well as polarized light microscopy and assays which assess structural integrity (collagen content through collagenase digestion and hydroxyproline assay) and biochemical composition (glycosaminoglycan content through dimethylmethylene blue assay following chondroitinase ABC treatment). In addition to histological validation, biomechanical validation will be performed through tensile and indentation testing. In the final aim of this project, the optimized and validated sequences will be used to characterize the Achilles tendon in asymptomatic volunteers as well as symptomatic patients with tendinosis (overuse), traumatic tendon tears, and psoriatic arthropathy. Comparison of validated UTE sequences will be made across these groups along with assessments for pain and function. It is evident that this responds directly to the need for improved diagnosis and therapeutic monitoring of tendon and enthesis diseases in a globally aging population and an increasing veteran population with injuries incurred during active duty. PUBLIC HEALTH RELEVANCE: With a globally aging population and an increasing veteran population with injuries incurred during active duty, tendon pathology and its impact on daily life after service is an established reality. However, non-invasive evaluation of tendon pathology is challenging and therefore critical assessment of the efficacy of the various therapies available is lacking. The purpose of this study is to optimize and implement novel MR pulse sequences to evaluate tendons in a non-invasive fashion. After validating and optimizing this novel technique, these sequences will be translated to clinical use to assess differences among damaged tendons due to repetitive strain injuries, acute trauma, and acquired or inherited diseases. Ultimately this technique can be applied to monitor and assess different therapeutic regimens for tendon disease.